Variant chr12-49974487-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001652.4(AQP6):c.561+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.00133 in 1,598,516 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 10 hom. )

Consequence

AQP6
NM_001652.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.9987

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

AQP6 (HGNC:639): (aquaporin 6) The protein encoded by this gene is an aquaporin protein, which functions as a water channel in cells. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). This protein is specific for the kidney. This gene and related family members AQP0, AQP2, and AQP5 reside in a cluster on chromosome 12q13. [provided by RefSeq, Jul 2008]

AQP6 links:

LOC105369764 (HGNC:):

LOC105369764 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-49974487-G-A is Benign according to our data. Variant chr12-49974487-G-A is described in ClinVar as [Benign]. Clinvar id is 787925.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00723 (1101/152334) while in subpopulation AFR AF= 0.0258 (1073/41566). AF 95% confidence interval is 0.0245. There are 13 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP6	NM_001652.4 linkuse as main transcript	c.561+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000315520.10	NP_001643.2
LOC105369764	XR_001749143.2 linkuse as main transcript	n.208+811C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
AQP6	ENST00000315520.10 linkuse as main transcript	c.561+5G>A	splice_donor_5th_base_variant, intron_variant	1	NM_001652.4	ENSP00000320247	P1
AQP6	ENST00000489786.5 linkuse as main transcript	n.2980+5G>A	splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant	1
AQP6	ENST00000551733.5 linkuse as main transcript	c.39+5G>A	splice_donor_5th_base_variant, intron_variant	3		ENSP00000449830

Frequencies

GnomAD3 genomes

AF:

0.00722

AC:

1099

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00196

AC:

470

AN:

239502

Hom.:

AF XY:

0.00140

AC XY:

181

AN XY:

129296

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000706

AC:

1021

AN:

1446182

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

424

AN XY:

717746

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000473

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000907

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00723

AC:

1101

AN:

152334

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

485

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00431

Hom.:

Bravo

AF:

0.00832

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over